NR 566 Final Exam Study Guide
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NR566 Week 5 Study Outline
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Chapter 18: DrugsAffecting the Hematopoietic System
i i i i i i
• Know ithe ipharmacodynamics, ipharmacotherapeutics iclinical iuse, idrug iinteractions iand iadverse idrug
ireactions ifor:
Anticoagulants
• Pharmacodynamics
• Oral ianticoagulants isuch ias iwarfarin i(Coumadin) iinhibit ithe ihepatic isynthesis iof iseveral iclotting ifactors,
iincluding ifactor iX. i
• Heparin iinhibits ithe iactivity iof iseveral iactivated iclotting ifactors iby iaccelerating ithe iactivity iof
iantithrombin iIII. i
• LMWH ienoxaparin i(Lovenox) ipotentiates ithe iactivity iof iantithrombin iIII iand iinactivates ifactors iXa iand
iIIa i(thrombin). i
• Dabigatran i(Pradaxa) iis ia idirect ithrombin iinhibitor. i
• Thrombin iis irequired ifor ithe iconversion iof ifibrinogen ito ifibrin iin ithe iclotting icascade,
ithus idabigatran's iinhibition iof ithrombin iprevents ithrombi ifrom iforming. i
• Fondaparinux i(Arixtra) iis ia iselective iinhibitor iof iantithrombin iIII iand ia ifactor iXa iinhibitor. i
• Rivaroxaban i(Xarelto) ian ianticoagulant, iis ia ihighly iselective ifactor iXa iinhibitor ithat iinhibits ithrombin i
i formation iand ithe idevelopment iof ithrombi. i
• Apixaban i(Eliquis) iis ia iselective iinhibitor iof ifactor iXa.
• Aspirin iantagonizes ithe icyclooxygenase ipathway iand iinterferes iwith iplatelet iaggregation.
• NSAIDs ihave ithis isame iaction. i
• NSAIDs iare inot iused ias iantiplatelet idrugs, ibut ithis iexplains iwhy iconcurrent iuse iwith
ianticoagulants iis icontraindicated
• Ticlopidine i(Ticlid) iand iclopidogrel i(Plavix) ireduce iplatelet iaggregation iby iinhibiting ithe iADP ipathway
iof iplatelets. i
• Unlike iaspirin, ithey ihave ino ieffect ion iprostaglandin imetabolism. i
• Ticagrelor i(Brilinta) ireversibly iinteracts iwith ithe iplatelet iP2Y12 iADP-receptor ito iprevent iplatelet
iactivation. i
• Vorapaxar i(Zontivity) iis ia iprotease-activated ireceptor-1 i(PAR-1) iantagonist, iinhibiting ithrombin-induced
iand ithrombin ireceptor iagonist ipeptide-induced iplatelet iaggregation
• Pharmacotherapeutics:
• Precautions iand iContraindications
• All ianticoagulants iare icontraindicated ifor ipatients iwho iare ihypersensitive ito ithe idrug ior iactively
ibleeding ior iwho ihave ihemophilia, ithrombocytopenia, isevere iHTN, iintracranial ihemorrhage, iinfective
iendocarditis, iactive ituberculosis, ior iulcerative ilesions iof ithe iGI itract. i
• Heparins iare icontraindicated iin iadvanced ihepatic ior irenal idisease. i
• They imay ibe iused iin ipatients iwho iare iactively ibleeding ito itreat iDIC i
• Heparin iis iPregnancy iCategory iC: istillbirth, iprematurity
, • Some iheparin ipreparations icontain ibenzyl ialcohol: iknown ito icause i“gasping isyndrome”: i
• fatal itoxicity iin ineonates
• Hyperkalemia imay idevelop
• Use ifor ipatient iwith iDM ior irenal iinsufficiency irequires icare iand ifrequent imonitoring iof iaPTT
• Has ibeen iassociated iwith ifatal imedication ierrors ir/t idifferent istrengths iof ipreparations
• JCo: ianticoagulant itherapy iis ia iNational ipatient iSafety iGoal: iplan iin iplace iat ieach ifacility ito
ireduce ipatient iharm
• LMWHs iare icontraindicated ifor ipatients iwith iallergies ito ipork, isulfites, ior ibenzyl ialcohol; iuncontrolled
ibleeding; iand iin ipatients iwho ihave iantiplatelet iantibodies
• Renal iimpairment: icautious iuse
• Body iweight iless ithan i50 ikg iassociated iwith iincreased ir/f ibleeding:
• enoxaparin idose iadjustment
• Cautious iuse: iuntreated iHTN, iretinopathy i(HTN ior iDM icaused), isevere iliver idisease, irecent iHx
iof iulcer, ior imalignancy
• Not iused ifor ithromboprophylaxis iin ipatients iwith imechanical iheart ivalues: iespecially ipregnant
i(r/f iheart ivalue ithrombosis)
• Enoxaparin: iPreg iCat iB, itinzaparin: iteratogenicity iand ifetal ideath, ifondaparinux: iPreg iB
• First iline idrug ifor iwomen iwho irequire iantithrombotic itherapy iduring ipregnancy: iLMWH
• Pharmacokinetics iof iLMWH iis ialtered iduring ipregnancy
• Warfarin
• Hepatic idysfunction ipotentiates iresponse ithrough iimpaired isynthesis iof icoagulation ifactors
• Use iwith icaution: iHypermetabolic istates iproduced iby ifever ior ihyperthyroidism iincrease
iresponsiveness ito iwarfarin:
• r/t iincreased icatabolism iof ivit iK idependent icoagulation ifactors
• Increased ir/f ibleeding iin iolder iadults
• Caution iuse ibased ion ibalance ibetween ipotential ifor idecreased ir/f ithromboembolism iand
ithe irisk ifor ibleeding iespecially iin ithose iwith idementia ior isevere icognitive iimpairment:
iHx iof ithree ifalls iin ithe iprevious iyear ior irecurrent iinjurious ifalls, iuncontrolled iHTN, ior
inon-adherent ior iunreliable
• Warfarin iis iPregnancy iCategory iX: iCrosses iplacenta iand ican icause ihemorrhagic idisorders iin
ithe ifetus iand iserious ibirth idefects
• Safe iduring ilactation
• Rivaroxaban i(Xarelto): iBlack-Box iWarning: ipremature idiscontinuation iof ianticoagulants iincluding
irivaroxaban imay ilead ito ithrombotic ievents. i
• An iincreased irisk iof istroke iis iseen iin ipatients iwith iatrial ifibrillation iwhen itransitioning ito
iwarfarin i
• Rivaroxaban iis iPregnancy iCategory iC iand iis inot irecommended ifor iuse iin ipregnant iwomen.
• Apixaban i(Eliquis): iBlack iBox iwarning ipremature idiscontinuation ileading ito ithrombotic ievents
• Although ithere iare ino iwell-controlled istudies: iPregnancy iCategory iB
• Hypersensitivity ito iaspirin iand icross-sensitivity iwith iNSAIDs imay ioccur, icontraindicating ithe idrug
• Aspirin ihypersensitivity iis imore iprevalent iin ipatients iwith iasthma, inasal ipolyps, ior ichronic
iurticaria. i
• Reye isyndrome ihas ibeen iassociated iwith iits iuse iin ichildren iand iteenagers iwho ihave iinfluenza ior
ichickenpox.
• Reversible ihepatotoxicity ihas ioccurred
• Use iwith icaution iin iliver idamage, ipreexisting ihypoprothrombinemia, ior ivit iK ideficiency i
• Preg iCat iC iand iCat iD iin ithird itrimester
• Avoid iduring ilactation
• Clopidogrel iand iticlopidine: isevere ihepatic idisease i(r/f ibleeding id/o), ido inot iuse iin ithese ipatients
• Not irecommended ifor ipatients iwith iGI id/o
• Preg iCategory iB
• Ticlopidine: iclearance iincreased iwith iage, iolder iadults iincreased isensitivity ito ithis idrug i(closely
, imonitor ior iADRs)
• Older iadults: iincreased ilevels iof iclopidogrel: ino idosage iadjustments
• In iolder iadults iclopidogrel iis ia isafer idrug
• Ticlopidine: ielevations iin icholesterol iand iTC iwithin i1 imonth iof itherapy: ifactor iin iHLD
• Ticagrelor: iBlack-Box iWarning ito inot iuse iin ia ipatient iwith iactive ipathological ibleeding ior ihistory iof
iintracranial ihemorrhage. i
• Ticagrelor ishould ibe idiscontinued i5 idays iprior ito iany isurgery.
• Dabigatran: iBlack-Box iWarning iconcerning idiscontinuation iincreasing irisk iof ithrombotic ievents.
• There iis ino ireversal iagent iavailable ifor idabigatran
• Vorapaxar: iBlack-Box iWarning ito inot iuse iin ipatients iwith ia ihistory iof istroke, iTIA, iintracranial
ihemorrhage, ior iactive ipathological ibleeding. i
• Vorapaxar iis iPregnancy iCategory iB, iwith ino icongenital imalformations ifound iin ianimal istudies
• ADRs
• All ianticoagulants: iexcessive ibleeding
• Risk iis ihigher iearly iin itherapy, iwith iwide ifluctuations iin iaPTT ior iINR, iand iolder iadults
i(especially iwomen iover i60)
• Heparins: icause ithrombocytopenia iand ianemia
• More ilikely iwith ibovine ithan iwith iporcine
• Early ithrombocytopenia i2 ito i3 idays iafter istarting itherapy iand idelayed iforms i7 ito
i12 idays
• Platelet ibelow i100,000: id/c iheparin
• Enoxaparin iantidote: iprotamine isulfate i1 img ifor ieach img iof ienoxaparin
idalteparin iand itinzaparin: i1 img ifor ieach i100 ianti-Xa iIUs iof idalteparin
• Slow iIV iinjection
• Fondaparinux: ino iknown iantidote
• Heparin ihas ia ishort ihalf-life: iTx iis iusually id/c iof ithe idrug
• Protamine isulfate iantidote ifor iheparin iOD
• Warfarin: itoxicity iand iOD iTx iwithholding ione ior imore idoses
• Or i1 ito i10 img iof ivitamin iK iis ithe iantidote ifor iminor ibleeding
• 5 ito i50 imay ibe iused ifor ifrank ibleeding
• Hemorrhagic iskin inecrosis iin iwomen iand icyanotic itoes iin imen ihave ibeen ireported
• r/t itransient iinhibition iin iproteins iS iand iC
• Allergic ireactions: isymmetrical, imaculopapular, ierythematous ilesions
• Some iare iisolated iand isome iconfluent: iface, ineck, iand itorso
• May inot iappear iuntil i8 ito i10 idays
• Ribaroxaban: ibleeding iis imajor iADR
• No ireversal iagent
• Back ipain, iupper iABD ipain, iosteoarthritis, idyspepsia, iand ifatigue
• Apixaban: ibleeding
• No ireversal iagent
• ASA: igastric ierosions: iincreased ir/f iserious iupper iGI ibleeding
• More ilikely iwhen iused iin icombo iwith iother ianticoags isuch ias iwarfarin
• Salicylism i(tinnitus) i: iserum ilevels iabove i200 imcg/mL
• Toxicity: itinnitus, iHA, ihyperventilation, iagitation, iconfusion, ilethargy, idiarrhea, iand
isweating
• Ticagrelor: ibleeding
• Dyspnea: isometimes iimproves iwith iuse ior imust ibe id/c
• HA, icough, idizziness, iand inausea
• Ticlopidine: ireversible ineutropenia iat i3 iweeks ito i3 imonths iafter iinitiation iof itherapy
• Severe ineutropenia i(<450) ior ithrombocytopenia i(<80,000) id/c idrug
• Clopidogrel: iADRs isimilar ito iASA, isafe iand ieffective
, • Dabigatran: ibleeding
• GI iADRs: idyspepsia iand igastritis-like isymptoms
• Angioedema iand ithrombocytopenia
• Vorapaxar: ibleeding
• Anemia, idepression, iand irashes ior ieruptions
• Drug iInteractions
• Cephalosporins iand iPCNs igiven iparenterally iassociated iwith icoagulopathies, iincreased ir/f ibleeding
iwhen igiven iwith iHeparin
• Second iand ithird igen icephalosporins iand ihigh idoses iof iPCNs: iincreased ir/f ibleeding iwith iWarfarin
• Drugs ithat iaffect iplatelet ifunctioning ior icause ihypoprothrombinemia i(ASA, iNSAIDS, idipyridamole,
iquinidine, iand ivalproic iacid: iincreased ir/f ibleeding
• Heparin iand iLMWHs: isimilar idrug iinteractions: ialso iinteract iwith iantiplatelets iincluding iNSAIDS iand
idextran
• Foods ican ieffect ianticoags
• Warfarin: imany idrug iinteractions iand iincreased iINR imonitoring iwithin i4 ito i7 idays iwhen iother idrugs iare
istarted ior istopped ieven iABX
• Vit iK: iantagonistic iinteraction iwith iwarfarin: idecreases ieffectiveness
• Inhibitors iof iCYP i1A2, iCYP i2C9, ior iCYP i3A4 iincrease ieffect iof iwarfarin
• Inhibitors idecrease ithe ieffectiveness iof iwarfarin
• Interacts iwith iany iother idrug ithat iincreased ibleeding: ianticoags, iantiplatelets, iNSAIDS iand
iSSRIs
• ABX iand iantifungals imay iaffect iINR
• Herbal iProductions imay iincrease ibleeding: iginkgo ibiloba iand igarlic
• Decrease ieffectiveness: iSt iJohn’s iwort, iginseng, iand icoenzyme iQ10
• May iinfluence imetabolism iof iwarfarin: iSt iJohn’s iwort, iechinacea, iginkgo, igoldenseal, iAND
iGRAPEFRUIT iJUICE
• Dabigatran: irifampin i(decreased ilevels iof idabigatran)
• Dronedarone iincreased idabigatran ilevels iby i70 ito i150%
• CCB iverapamil: iincreases idabigatran
• Amiodarone iincreases idabigatran
• Clopidogrel iincreases idabigatran
• Ticagrelor: imetabolized iby iCYP i3A4: iavoid istrong iinhibitors iketoconazole, iitraconazole, ivoriconazole,
iclarithromycin, inefazodone, iritonavir, isaquinavir, inelfinavir, iindinavir, iatazanavir, iand itelithromycin
• Avoid iinducers: irifampin, idexamethasone, iphenytoin icarbamazepine, iand iphenobarbital
• Vorapaxar: iavoid iwith iCYP3A iinhibitors
• Avoid iuse iof iinducers i(rifampin, icarbamazepine, iSt iJohn’s iWort, iand iphenytoin
• Clinical iUse iand iDosing
Prevention iand iTreatment iof iThromboembolism
• Warfarin: idrug iof ichoice ifor iprevention iof ivenous ithrombosis, isystemic ithrombosis, iand ipulmonary iembolism
o For iprevention: igive idose isufficient ifor iINR ibetween i2 iand i3
o Beginning idose iis i10 img idaily ifor ithe ifirst i2 idays iwith ia irecheck iof iINR iin itwo ito ithree idoses
o ICSI iguidelines: irecommend istarting iwarfarin iat i5 img/day iwith ia irange iof i2.5 img ito i7.5 img/day
o Further idosing iis ibased ion iINR
o Lower iinitiation idoses ifor:
▪ Older ithan i75
▪ Multiple icomorbid iconditions
▪ Poor inutrition i(low ialbumin)
i i i i i
NR566 Week 5 Study Outline
i i i i
Chapter 18: DrugsAffecting the Hematopoietic System
i i i i i i
• Know ithe ipharmacodynamics, ipharmacotherapeutics iclinical iuse, idrug iinteractions iand iadverse idrug
ireactions ifor:
Anticoagulants
• Pharmacodynamics
• Oral ianticoagulants isuch ias iwarfarin i(Coumadin) iinhibit ithe ihepatic isynthesis iof iseveral iclotting ifactors,
iincluding ifactor iX. i
• Heparin iinhibits ithe iactivity iof iseveral iactivated iclotting ifactors iby iaccelerating ithe iactivity iof
iantithrombin iIII. i
• LMWH ienoxaparin i(Lovenox) ipotentiates ithe iactivity iof iantithrombin iIII iand iinactivates ifactors iXa iand
iIIa i(thrombin). i
• Dabigatran i(Pradaxa) iis ia idirect ithrombin iinhibitor. i
• Thrombin iis irequired ifor ithe iconversion iof ifibrinogen ito ifibrin iin ithe iclotting icascade,
ithus idabigatran's iinhibition iof ithrombin iprevents ithrombi ifrom iforming. i
• Fondaparinux i(Arixtra) iis ia iselective iinhibitor iof iantithrombin iIII iand ia ifactor iXa iinhibitor. i
• Rivaroxaban i(Xarelto) ian ianticoagulant, iis ia ihighly iselective ifactor iXa iinhibitor ithat iinhibits ithrombin i
i formation iand ithe idevelopment iof ithrombi. i
• Apixaban i(Eliquis) iis ia iselective iinhibitor iof ifactor iXa.
• Aspirin iantagonizes ithe icyclooxygenase ipathway iand iinterferes iwith iplatelet iaggregation.
• NSAIDs ihave ithis isame iaction. i
• NSAIDs iare inot iused ias iantiplatelet idrugs, ibut ithis iexplains iwhy iconcurrent iuse iwith
ianticoagulants iis icontraindicated
• Ticlopidine i(Ticlid) iand iclopidogrel i(Plavix) ireduce iplatelet iaggregation iby iinhibiting ithe iADP ipathway
iof iplatelets. i
• Unlike iaspirin, ithey ihave ino ieffect ion iprostaglandin imetabolism. i
• Ticagrelor i(Brilinta) ireversibly iinteracts iwith ithe iplatelet iP2Y12 iADP-receptor ito iprevent iplatelet
iactivation. i
• Vorapaxar i(Zontivity) iis ia iprotease-activated ireceptor-1 i(PAR-1) iantagonist, iinhibiting ithrombin-induced
iand ithrombin ireceptor iagonist ipeptide-induced iplatelet iaggregation
• Pharmacotherapeutics:
• Precautions iand iContraindications
• All ianticoagulants iare icontraindicated ifor ipatients iwho iare ihypersensitive ito ithe idrug ior iactively
ibleeding ior iwho ihave ihemophilia, ithrombocytopenia, isevere iHTN, iintracranial ihemorrhage, iinfective
iendocarditis, iactive ituberculosis, ior iulcerative ilesions iof ithe iGI itract. i
• Heparins iare icontraindicated iin iadvanced ihepatic ior irenal idisease. i
• They imay ibe iused iin ipatients iwho iare iactively ibleeding ito itreat iDIC i
• Heparin iis iPregnancy iCategory iC: istillbirth, iprematurity
, • Some iheparin ipreparations icontain ibenzyl ialcohol: iknown ito icause i“gasping isyndrome”: i
• fatal itoxicity iin ineonates
• Hyperkalemia imay idevelop
• Use ifor ipatient iwith iDM ior irenal iinsufficiency irequires icare iand ifrequent imonitoring iof iaPTT
• Has ibeen iassociated iwith ifatal imedication ierrors ir/t idifferent istrengths iof ipreparations
• JCo: ianticoagulant itherapy iis ia iNational ipatient iSafety iGoal: iplan iin iplace iat ieach ifacility ito
ireduce ipatient iharm
• LMWHs iare icontraindicated ifor ipatients iwith iallergies ito ipork, isulfites, ior ibenzyl ialcohol; iuncontrolled
ibleeding; iand iin ipatients iwho ihave iantiplatelet iantibodies
• Renal iimpairment: icautious iuse
• Body iweight iless ithan i50 ikg iassociated iwith iincreased ir/f ibleeding:
• enoxaparin idose iadjustment
• Cautious iuse: iuntreated iHTN, iretinopathy i(HTN ior iDM icaused), isevere iliver idisease, irecent iHx
iof iulcer, ior imalignancy
• Not iused ifor ithromboprophylaxis iin ipatients iwith imechanical iheart ivalues: iespecially ipregnant
i(r/f iheart ivalue ithrombosis)
• Enoxaparin: iPreg iCat iB, itinzaparin: iteratogenicity iand ifetal ideath, ifondaparinux: iPreg iB
• First iline idrug ifor iwomen iwho irequire iantithrombotic itherapy iduring ipregnancy: iLMWH
• Pharmacokinetics iof iLMWH iis ialtered iduring ipregnancy
• Warfarin
• Hepatic idysfunction ipotentiates iresponse ithrough iimpaired isynthesis iof icoagulation ifactors
• Use iwith icaution: iHypermetabolic istates iproduced iby ifever ior ihyperthyroidism iincrease
iresponsiveness ito iwarfarin:
• r/t iincreased icatabolism iof ivit iK idependent icoagulation ifactors
• Increased ir/f ibleeding iin iolder iadults
• Caution iuse ibased ion ibalance ibetween ipotential ifor idecreased ir/f ithromboembolism iand
ithe irisk ifor ibleeding iespecially iin ithose iwith idementia ior isevere icognitive iimpairment:
iHx iof ithree ifalls iin ithe iprevious iyear ior irecurrent iinjurious ifalls, iuncontrolled iHTN, ior
inon-adherent ior iunreliable
• Warfarin iis iPregnancy iCategory iX: iCrosses iplacenta iand ican icause ihemorrhagic idisorders iin
ithe ifetus iand iserious ibirth idefects
• Safe iduring ilactation
• Rivaroxaban i(Xarelto): iBlack-Box iWarning: ipremature idiscontinuation iof ianticoagulants iincluding
irivaroxaban imay ilead ito ithrombotic ievents. i
• An iincreased irisk iof istroke iis iseen iin ipatients iwith iatrial ifibrillation iwhen itransitioning ito
iwarfarin i
• Rivaroxaban iis iPregnancy iCategory iC iand iis inot irecommended ifor iuse iin ipregnant iwomen.
• Apixaban i(Eliquis): iBlack iBox iwarning ipremature idiscontinuation ileading ito ithrombotic ievents
• Although ithere iare ino iwell-controlled istudies: iPregnancy iCategory iB
• Hypersensitivity ito iaspirin iand icross-sensitivity iwith iNSAIDs imay ioccur, icontraindicating ithe idrug
• Aspirin ihypersensitivity iis imore iprevalent iin ipatients iwith iasthma, inasal ipolyps, ior ichronic
iurticaria. i
• Reye isyndrome ihas ibeen iassociated iwith iits iuse iin ichildren iand iteenagers iwho ihave iinfluenza ior
ichickenpox.
• Reversible ihepatotoxicity ihas ioccurred
• Use iwith icaution iin iliver idamage, ipreexisting ihypoprothrombinemia, ior ivit iK ideficiency i
• Preg iCat iC iand iCat iD iin ithird itrimester
• Avoid iduring ilactation
• Clopidogrel iand iticlopidine: isevere ihepatic idisease i(r/f ibleeding id/o), ido inot iuse iin ithese ipatients
• Not irecommended ifor ipatients iwith iGI id/o
• Preg iCategory iB
• Ticlopidine: iclearance iincreased iwith iage, iolder iadults iincreased isensitivity ito ithis idrug i(closely
, imonitor ior iADRs)
• Older iadults: iincreased ilevels iof iclopidogrel: ino idosage iadjustments
• In iolder iadults iclopidogrel iis ia isafer idrug
• Ticlopidine: ielevations iin icholesterol iand iTC iwithin i1 imonth iof itherapy: ifactor iin iHLD
• Ticagrelor: iBlack-Box iWarning ito inot iuse iin ia ipatient iwith iactive ipathological ibleeding ior ihistory iof
iintracranial ihemorrhage. i
• Ticagrelor ishould ibe idiscontinued i5 idays iprior ito iany isurgery.
• Dabigatran: iBlack-Box iWarning iconcerning idiscontinuation iincreasing irisk iof ithrombotic ievents.
• There iis ino ireversal iagent iavailable ifor idabigatran
• Vorapaxar: iBlack-Box iWarning ito inot iuse iin ipatients iwith ia ihistory iof istroke, iTIA, iintracranial
ihemorrhage, ior iactive ipathological ibleeding. i
• Vorapaxar iis iPregnancy iCategory iB, iwith ino icongenital imalformations ifound iin ianimal istudies
• ADRs
• All ianticoagulants: iexcessive ibleeding
• Risk iis ihigher iearly iin itherapy, iwith iwide ifluctuations iin iaPTT ior iINR, iand iolder iadults
i(especially iwomen iover i60)
• Heparins: icause ithrombocytopenia iand ianemia
• More ilikely iwith ibovine ithan iwith iporcine
• Early ithrombocytopenia i2 ito i3 idays iafter istarting itherapy iand idelayed iforms i7 ito
i12 idays
• Platelet ibelow i100,000: id/c iheparin
• Enoxaparin iantidote: iprotamine isulfate i1 img ifor ieach img iof ienoxaparin
idalteparin iand itinzaparin: i1 img ifor ieach i100 ianti-Xa iIUs iof idalteparin
• Slow iIV iinjection
• Fondaparinux: ino iknown iantidote
• Heparin ihas ia ishort ihalf-life: iTx iis iusually id/c iof ithe idrug
• Protamine isulfate iantidote ifor iheparin iOD
• Warfarin: itoxicity iand iOD iTx iwithholding ione ior imore idoses
• Or i1 ito i10 img iof ivitamin iK iis ithe iantidote ifor iminor ibleeding
• 5 ito i50 imay ibe iused ifor ifrank ibleeding
• Hemorrhagic iskin inecrosis iin iwomen iand icyanotic itoes iin imen ihave ibeen ireported
• r/t itransient iinhibition iin iproteins iS iand iC
• Allergic ireactions: isymmetrical, imaculopapular, ierythematous ilesions
• Some iare iisolated iand isome iconfluent: iface, ineck, iand itorso
• May inot iappear iuntil i8 ito i10 idays
• Ribaroxaban: ibleeding iis imajor iADR
• No ireversal iagent
• Back ipain, iupper iABD ipain, iosteoarthritis, idyspepsia, iand ifatigue
• Apixaban: ibleeding
• No ireversal iagent
• ASA: igastric ierosions: iincreased ir/f iserious iupper iGI ibleeding
• More ilikely iwhen iused iin icombo iwith iother ianticoags isuch ias iwarfarin
• Salicylism i(tinnitus) i: iserum ilevels iabove i200 imcg/mL
• Toxicity: itinnitus, iHA, ihyperventilation, iagitation, iconfusion, ilethargy, idiarrhea, iand
isweating
• Ticagrelor: ibleeding
• Dyspnea: isometimes iimproves iwith iuse ior imust ibe id/c
• HA, icough, idizziness, iand inausea
• Ticlopidine: ireversible ineutropenia iat i3 iweeks ito i3 imonths iafter iinitiation iof itherapy
• Severe ineutropenia i(<450) ior ithrombocytopenia i(<80,000) id/c idrug
• Clopidogrel: iADRs isimilar ito iASA, isafe iand ieffective
, • Dabigatran: ibleeding
• GI iADRs: idyspepsia iand igastritis-like isymptoms
• Angioedema iand ithrombocytopenia
• Vorapaxar: ibleeding
• Anemia, idepression, iand irashes ior ieruptions
• Drug iInteractions
• Cephalosporins iand iPCNs igiven iparenterally iassociated iwith icoagulopathies, iincreased ir/f ibleeding
iwhen igiven iwith iHeparin
• Second iand ithird igen icephalosporins iand ihigh idoses iof iPCNs: iincreased ir/f ibleeding iwith iWarfarin
• Drugs ithat iaffect iplatelet ifunctioning ior icause ihypoprothrombinemia i(ASA, iNSAIDS, idipyridamole,
iquinidine, iand ivalproic iacid: iincreased ir/f ibleeding
• Heparin iand iLMWHs: isimilar idrug iinteractions: ialso iinteract iwith iantiplatelets iincluding iNSAIDS iand
idextran
• Foods ican ieffect ianticoags
• Warfarin: imany idrug iinteractions iand iincreased iINR imonitoring iwithin i4 ito i7 idays iwhen iother idrugs iare
istarted ior istopped ieven iABX
• Vit iK: iantagonistic iinteraction iwith iwarfarin: idecreases ieffectiveness
• Inhibitors iof iCYP i1A2, iCYP i2C9, ior iCYP i3A4 iincrease ieffect iof iwarfarin
• Inhibitors idecrease ithe ieffectiveness iof iwarfarin
• Interacts iwith iany iother idrug ithat iincreased ibleeding: ianticoags, iantiplatelets, iNSAIDS iand
iSSRIs
• ABX iand iantifungals imay iaffect iINR
• Herbal iProductions imay iincrease ibleeding: iginkgo ibiloba iand igarlic
• Decrease ieffectiveness: iSt iJohn’s iwort, iginseng, iand icoenzyme iQ10
• May iinfluence imetabolism iof iwarfarin: iSt iJohn’s iwort, iechinacea, iginkgo, igoldenseal, iAND
iGRAPEFRUIT iJUICE
• Dabigatran: irifampin i(decreased ilevels iof idabigatran)
• Dronedarone iincreased idabigatran ilevels iby i70 ito i150%
• CCB iverapamil: iincreases idabigatran
• Amiodarone iincreases idabigatran
• Clopidogrel iincreases idabigatran
• Ticagrelor: imetabolized iby iCYP i3A4: iavoid istrong iinhibitors iketoconazole, iitraconazole, ivoriconazole,
iclarithromycin, inefazodone, iritonavir, isaquinavir, inelfinavir, iindinavir, iatazanavir, iand itelithromycin
• Avoid iinducers: irifampin, idexamethasone, iphenytoin icarbamazepine, iand iphenobarbital
• Vorapaxar: iavoid iwith iCYP3A iinhibitors
• Avoid iuse iof iinducers i(rifampin, icarbamazepine, iSt iJohn’s iWort, iand iphenytoin
• Clinical iUse iand iDosing
Prevention iand iTreatment iof iThromboembolism
• Warfarin: idrug iof ichoice ifor iprevention iof ivenous ithrombosis, isystemic ithrombosis, iand ipulmonary iembolism
o For iprevention: igive idose isufficient ifor iINR ibetween i2 iand i3
o Beginning idose iis i10 img idaily ifor ithe ifirst i2 idays iwith ia irecheck iof iINR iin itwo ito ithree idoses
o ICSI iguidelines: irecommend istarting iwarfarin iat i5 img/day iwith ia irange iof i2.5 img ito i7.5 img/day
o Further idosing iis ibased ion iINR
o Lower iinitiation idoses ifor:
▪ Older ithan i75
▪ Multiple icomorbid iconditions
▪ Poor inutrition i(low ialbumin)
